Lab Anim Res.
2023 Jun;39(2):165-171. 10.1186/s42826-023-00157-4.
SARS‑CoV‑2 Omicron variant causes brain infection with lymphoid depletion in a mouse COVID‑19 model
- Affiliations
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- 1Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, 1 Kangwondaehak‑Gil, Chuncheon‑si, Gangwon‑do 24341, South Korea
- 2Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul, South Korea
- 3Laboratory of Avian Diseases, BK21 Plus Program for Veterinary Science and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea
- 4Korea Mouse Phenotyping Center (KMPC), Seoul National University, Seoul 08826, South Korea
- 5Laboratory of Developmental Biology and Genomics, Research Institute for Veterinary Science, and BK 21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul 08826, South Korea
- 6Avian Influenza Research and Diagnostic Division, Animal and Plant Quarantine Agency, Gimcheon 39660, South Korea
- 7Severance Biomedical Science Institute, Brain Kore a 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, South Korea
- 8Institute of Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, South Korea
- 9Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, South Korea
- 10Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, South Korea
- 11College of Pharmacy, Gachon University, Incheon, South Korea
- 12Laboratory of Veterinary Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 08826, South Korea
- KMID: 2544279
- DOI: http://doi.org/10.1186/s42826-023-00157-4
Abstract
- Background
The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection.
Results
K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection.
Conclusion
Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.
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